Our research has as its goal the elucidation of the molecular mechanisms of carcinogenesis. Three major agents of carcinogenesis--physical (radiation), chemical (particularly benzo(a)pyrene), and biological (both DNA virus such as SV40 and RNA virus such as murine sarcoma and Rous sarcoma)--are being employed on a variety of cell lines. Not only do we seek to understand the biochemical and biophysical changes which occur during a normal cell cycle, but eventually what these changes are in cells transformed by one or another of the above agents. The factors which we are presently examining, in addition to the growth factors in the medium, are such matters as metabolism of carbohydrates as well as membrane composition and changes. The mechanism of the transformation by a DNA virus seems to involve integration of certain viral DNA information. A similar process is presumed to occur with an RNA oncogenic virus, preceded by a copy of the RNA into DNA with an RNA-dependent DNA polymerase (RDP). Isolation and characterization of this RDP is among the several parameters of the normal and transformed cell with which we are concerned. Furthermore, in pursuit of this investigation with a presumed specific inhibitor of the RDP, a system has been found in which cells already transformed with Rous sarcoma virus seem to be more sensitive to the inhibitor than they are prior to transformation. This requires an additional unknown step to differentiate the two cell lines. Search continues for this factor as well as the membrane and other changes.